This research proposal represents a multidisciplinary approach to a number of fundamental problems of lymphocyte biology. The focus of attack will be the lymphocyte surface. We will make use of a variety of experimental approaches drawn from the fields of immunochemistry, cellular immunology, biochemistry, cell biology and virology. Using new methods for isolating subclasses of T and B lymphocytes and labeling of cell surface macromolecules, we will study the nature of the antigen recognition unit on the T cell surface, the biochemical nature and mode of action of signals produced by stimulated T cells and the biochemistry and biology of the antigens Thy-1 and TL. On B lymphocytes, we will study the regulation of cell surface IgM as well as the role of J chain in the polymerization exteriorization and/or secretion of IgM. Important macromolecules found on the surface of lymphocytes such as Ig and the gene products of Ir, H-2 and TL will be characterized biochemically and their synthesis, intracellular transport, insertion into the plasma membrane, release and degradation studied in order to explain their function in immunological reactions. In addition, we will do biochemical and ultrastructural studies to determine the topography and binding to the cell membrane of these macromolecules. The products of the H-2 and Ir genes will be characterized by immunochemical methods and peptide mapping to elucidate their genetic control. The role of the lymphocyte cell surface in virus-induced lymphocytic leukemia will be investigated. The attachment of virions to the lymphocyte plasma membrane will be studied to determine whether the host and tissue specific tropisms of viruses can be accounted for by cellular differences in virus receptor sites on the plasma membrane. We will isolate and characterize the virus receptor site for a murine leukemia virus.